With an increase in the population of senior citizens, development of pharmaceutical products that are effective for treatment of senile dementia has been strongly awaited in recent years. A typical senile dementia disease; i.e., Alzheimer's disease, is a neurodegenerative disease characterized by brain shrinkage, senile plaque deposition, and neurofibrillary changes. The configuration of amyloid β peptide is changed, and insoluble molecules resulting from fibrillogenesis caused by such change are deposited in nerve cells. Nerve cell death is induced by toxicity of the insoluble molecules, and Alzheimer's disease is then developed.
Amyloid β peptide (Aβ) is a degradation product resulting from a neuron amyloid precursor protein via cleavage with, for example, β secretase, and two types thereof; i.e., Aβ1-40 and Aβ1-42, are generated. Aβ1-42 more easily aggregates, and Aβ1-42 is reported to be more often correlated with diseases and neurotoxicity.
If the changes in amyloid β peptide configuration and the fibrillogenesis caused by the changes could be inhibited, development of Alzheimer's disease could be suppressed.
WO 2005/105998 discloses that a single-stranded antibody that has activity of binding specifically to Aβ1-42 and inhibiting the fibrillogenesis is useful as a preventive and/or therapeutic agent for Alzheimer's disease.
Since antibodies are high-molecular-weight proteins, disadvantageously, antibodies are expensive, the processes of production and purification thereof are laborious, and the stabilities of antibodies are insufficient.
The development of vaccines is a means for inducing such immune response in humans, and the most critical issue of concern is the substance to be used as an immunogen.
At present, many reports have been made regarding the use of peptides as vaccines for prevention and treatment of Alzheimer's disease; for example, use of part of a normal amyloid β amino acid sequence as an antigen (e.g., WO 2006/121656; G. G Kinney et al., A Novel anti-amyloid beta active vaccine approach for the treatment of Alzheimer's and related disorders, Neuro-degenerative Diseases, 4: supplement 1, p. 251, 2007) and use of a newly developed peptide sequence referred to as an amyloid β mimotope as an antigen (JP Patent Publication (kohyo) No. 2006-515876 A; M. Mandler et al., The AFFiR is mimotope vaccine: A novel approach for the treatment of AD, Neuro-degenerative Diseases, 4: supplement 1, p. 250, 2007).